Mdmafpea

[seananderson]

Methylenedioxymethylalphaflourophenethylamine

or just alphaflourophenethylamine

Would it work?

 

[ebola?]

What is your rationale for your question?

ebola

 

[seananderson]

it seems to me that amphetamine and mda compounds are active due to their similarity to dopamine. The alpha methyl produces stimulent effects and seems to prevent enzymatic attack. In the last few years tons of amphetamine substitutions have become quite popular, including Methylone, MBDB, 4FA, and quite a few others have been popular in the past. The only sub I have seen for alpha methyl is alpha ethyl, which is MBDB; and it seems that the stimulant effects are almost cancelled out in that case. Phenethylamine is virtually inactive on it's own, but add the methyl group and you have a very active compound indeed. Mescaline and the 2C compounds have a clean ethylamine group, but I suspect that the methoxy on the 2 position inhibits the enzymatic attack; and those compounds do not produce stimulent effects. So it seems that stimulent phenethylamines require the alpha methyl. Drugs are often fluorinated at biologically active positions to prevent breakdown at that position, so it would seem that alpha fluoro could serve the same role as alpha methyl in this case. Since amphetamines are so sensitive at this postition, a suitable replacement for alpha methyl could provide some interesting differences and the pharmacological properties could be worth studying. What do you think?

 

[sekio]

so it would seem that alpha fluoro could serve the same role as alpha methyl in this case.

I don't think so. SAR is not that simple, and fluorine is rather imilar to hydrogen in terms of properties as a substituent. Mescaline and the 2Cs are not pharmacologically active in the same way MDMA or amphetamine are, despite similar structures.

If you're wrong about stability and MAO chews this anyway then you will make HF and other gnarly products.

 

[seananderson]

Well that's a good point about hydrogen fluoride, definitely a possibility there. Still, I'd be curious about other subs at this point, considering what a dramatic difference there is just between the alpha methyl enantiomers. Elongation doesn't seem to be a good route. What about a carbonyl group here?

 

[vecktor]

Well that's a good point about hydrogen fluoride, definitely a possibility there. Still, I'd be curious about other subs at this point, considering what a dramatic difference there is just between the alpha methyl enantiomers. Elongation doesn't seem to be a good route. What about a carbonyl group here?

carbonyl in place of the alpha methyl gives an amide, the nitrogen is no longer basic and the substance will be inactive. carbonyl on the alpha methyl gives a reactive aldehyde which will undergo intermolecular condensation to make a cyclic dimer.

alpha alpha difluoro is a bioisostere of amide in peptide mimic design, but amide is not what is requird by amphetamine SAR.

 

[seananderson]

vecktor, thanks for the educated response. Seems there's not much that can be done here.

 

[Hammilton]

^ Probably not truly inactive. I think there are some depressants with similar structures.